Biologics Development, Bristol Myers Squibb Co , New Brunswick, NJ, USA.
MAbs. 2020 Jan-Dec;12(1):1763727. doi: 10.1080/19420862.2020.1763727.
The importance of speed to clinic for medicines that may address unmet medical needs puts pressure on product development timelines. Historically, both toxicology and first-in-human clinical materials are generated using the same clonal-derived cells to ensure safety and minimize any development risks. However, cell line development with single cell cloning is time consuming, and aggravated by the time needed to screen for a lead clone based on cell line stability and manufacturability. In order to achieve faster timelines, we have used pools of up to six clones for earlier production of drug substance for regulatory filing-enabling toxicology studies, and then the final single clone was selected for production of clinical materials. This approach was enabled by using platform processes across all stages of early development, including expression vectors, host cell lines, media, and production processes. Through comprehensive cell culture and product quality analysis, we demonstrated that the toxicology material was representative of the clinical material for all six monoclonal antibody programs evaluated. Our extensive development experience further confirmed that using a pool of clones for toxicology material generation is a reliable approach to shorten the early development timeline.
对于可能解决未满足医疗需求的药物,其快速进入临床的重要性给产品开发时间线带来了压力。从历史上看,毒理学和首次人体临床材料都是使用相同的克隆衍生细胞生成的,以确保安全性并将任何开发风险降到最低。然而,单细胞克隆的细胞系开发既耗时又复杂,而且还需要根据细胞系稳定性和可制造性筛选出先导克隆,这进一步延长了开发时间。为了实现更快的时间线,我们使用多达六个克隆的混合物来提前生产药物物质,以进行监管备案的毒理学研究,然后再选择最终的单个克隆来生产临床材料。这种方法通过在早期开发的所有阶段使用平台工艺实现,包括表达载体、宿主细胞系、培养基和生产工艺。通过全面的细胞培养和产品质量分析,我们证明了毒理学材料对于评估的所有六个单克隆抗体项目的临床材料都是具有代表性的。我们丰富的开发经验进一步证实,使用克隆混合物来生成毒理学材料是缩短早期开发时间线的可靠方法。